Ornithine Decarboxylase Inhibition: A Strategy to Combat Various Diseases

Mini Rev Med Chem. 2018;18(12):1008-1021. doi: 10.2174/1389557517666170927130526.

Abstract

Ornithine decarboxylase is the first enzyme in the polyamine biosynthetic pathway. It is the rate-limiting enzyme which is included during the change of ornithine to putrescine which is the first polyamine. Polyamines (putrescine, spermidine, spermine) are natural and synthetic compounds which contain two or more amino group. Polyamines are highly implicated in cellular functions such as cell growth & multiplication, DNA stabilization, gene transcription and translation, ion-channel activity, etc. Elevated levels of polyamines are found in highly proliferating tumor cells. Hence inhibition of this enzyme was found useful in cancer. α-DL-difluoromethylornithine(DFMO) (Eflornithine) an enzyme- activated irreversible inhibitor was the first of this type. However, its use as an anticancer agent did not continue for long due to various reasons. Polyamines have also been found to play an important role in other infectious microorganisms. Eflornithine is successfully used in diseases such as African sleeping sickness and is being researched against a number of tropical diseases. It is widely used against hirsutism in women. Various other product (putrescine) based analogs and transition state or PLP (cofactor) based analogs are being synthesized against diseases such as Leishmaniasis, Malaria and others discussed in the article.

Keywords: African sleeping sickness; antibiotic; cancer; malaria; ornithine decarboxylase; polyamines..

Publication types

  • Review

MeSH terms

  • Animals
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Humans
  • Leishmaniasis / drug therapy
  • Malaria / drug therapy
  • Neglected Diseases / drug therapy
  • Neglected Diseases / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Ornithine Decarboxylase / metabolism*
  • Ornithine Decarboxylase Inhibitors / chemistry
  • Ornithine Decarboxylase Inhibitors / pharmacology*

Substances

  • Antimalarials
  • Antineoplastic Agents
  • Ornithine Decarboxylase Inhibitors
  • Ornithine Decarboxylase